Intermittent Fasting Accompanying Chemotherapy in Gynecological Cancers (FIT2)

Intermittent Fasting Accompanying Chemotherapy in Gynecological Cancers - a Randomized, Controlled, Two-armed Intervention Study

The aim of this trial is an evaluation of the effectiveness of intermittent fasting as a supplementary therapy in patients with breast cancer and ovarian cancer in respect to quality of life, reduction of side effects and possible reduction in tumor progression.

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer; Ovarian Cancer
• Intervention / Treatment: Other: Fasting; Other: Vegan

Detailed Description

Chemotherapy (CT) is a basic element in the therapy of gynecological oncologic diseases besides surgery, antibody therapy, anti-hormonal therapy and radiation. The chemotherapeutic intervention can be experienced physically and psychologically as a severe stress due to unwanted acute and also relevant long term side effects. It is even possible that because of severe side effects the CT can not be continued and main goals of the therapy like tumor reduction or elimination can not be achieved. Except of some medicinal approaches (such as antiemetics) or therapeutic exercise, not many therapeutic approaches are known to help reduce CT induced side effects. Against this background it is important to identify and scientifically evaluate new approaches to reduce the side effects of CT. The aim of this study is to verify the effectiveness of intermittent fasting as a potentially helpful supportive therapy in CT. In a prior pilot study of our institute with 34 breast- and ovarian cancer patients showed beneficial effects of an intermittent fasting of 72-84 h parallel to the application of the CT (manuscript submitted in Cancer Science).

The results of this confirmatory study are therefore of potentially high clinical relevance for all chemotherapeutically treated patients.

Long term goal: This study can lead to the improvement of tolerance and effectiveness of chemotherapeutic tumor therapy through accompanying intense nutritional therapy interventions. Beyond that it can be the starting point of a following multi-center randomized controlled study.

A large variety of animal experimental studies as well as three smaller pilot studies suggest that intermittent fasting can reduce the unwanted side effects of CT and enhance the quality of life. It is being speculated that the anti-tumor effect of fasting is enhanced through the reduction of the Insulin-like growth factor-1 (IGF-1) and mTOR as well as p53-signalling molecules (differential stress resistance).

But it is still unclear whether the possible beneficial effect that intermittent fasting shows can only be reached by subtotal caloric restriction or a significant reduction of the intake of animal proteins and refined sugar could also cause a similar decrease in IGF-1.

Against this background this confirmatory study aims to test the hypothesis that CT in the adjuvant and neoadjuvant treatment of breast- and ovarian cancer is better tolerable under intermittent fasting than under a normo-caloric vegan and sugar-reduced diet.

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10117
    • Brustzentrum Charite Campus Mitte
  • Berlin, Germany, 10967
    • Vivantes Brustzentrum
  • Berlin, Germany, 13353
    • Charité Virchow Klinikum
  • Berlin, Germany, 14163
    • Brustzentrum Krankenhaus Waldfriede
  • Berlin, Germany, 14163
    • Charité Hochschulambulanz für Naturheilkunde am Immanuel Krankenhaus
  • Baden-Württemberg
    • Freiburg im Breisgau, Baden-Württemberg, Germany, 79085
      • Albert-Ludwigs-University of Freiburg
    • Ludwigsburg, Baden-Württemberg, Germany, 71640
      • Klinikum Ludwigsburg
  • Brandenburg
    • Potsdam, Brandenburg, Germany, 14467
      • Ernst-von-Bergmann Klinikum, Klinik für Gynäkologie und Geburtshilfe

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Diagnosed, gynecological, malignant tumor disease (non-metastatic ovarian or breast cancer).

Other inclusion criteria:

• Age 18-75 years
• Cancer is treated conventionally with an adjuvant or neo-adjuvant protocol with at least 4 CT cycles

The following CTs are considered for breast carcinoma:

• - (EC, Sparano) 4 x Epirubicin and Cyclophosphamide, followed by 12 cycles Paclitaxel weekly
• - (AC, Henderson) 4 x Doxorubicin, cyclophosphamide, followed by 4 cycles Docetaxel every three weeks

If the recruitment rate is not reached, further CT protocols can be accepted.

CT for patients with ovarian cancer: According to current protocols, at least 4 planned cycles. For the study a maximum of 8 cycles are considered (except therapy with Taxol).

Exclusion Criteria:

• Reduction in CT dose compared to usual dosage
• Excessive underweight (BMI <19kg / m2) or actual weight reduction > 3kg or > 5kg in the last 1 or 3 months.
• Pre-existing eating disorder (Anorexia nervosa, Bulimia)
• Renal insufficiency (creatinine> 2mg / dl)
• Severe disease or other disease with a significant reduction in mobility and overall vitality
• Diabetes mellitus
• No inclusion in other study protocol
• Lack of email address and Internet access (due to electronic CRF)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Fasting; 60-72 h-modified fasting (36-48 h before and 24 h after chemotherapy)	Other: Fasting; Patients follow a modified fasting regime of 60-72 h (36-48 h before and 24 h after CT) with a dietary energy supply of 350-400kcal per day with vegetable juices during the first four cycles of CT. During the rest of the CT cycles they will observe two days of caloric restriction (24 h before and after CT). Between CTs a mainly vegetarian diet will be performed and the patients are encouraged to follow a pattern of time restricted feeding with 14 h fasting over night at least for six days a week. The patients will receive an individual nutrition training by trained nutritionists.
Active Comparator: Vegan; 60-72 h-vegan diet (36-48 h before and 24 h after chemotherapy)	Other: Vegan; Patients follow a 60-72 h vegan diet with sugar restriction (36-48 h before and 24 h after CT) during the first four cycles of CT. During the rest of the CT cycles they will observe two days of vegan and sugar-restricted diet (24 h before and after CT). Between CTs a mainly vegetarian diet will be performed. The patients will receive an individual nutrition training by trained nutritionists.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
FACT-G	Summarized change of FACT-G score	Date of inclusion (baseline), day -2 and +7 at each chemotherapy (CT) in triweekly cycles/-2 days at each CT in weekly cycles and +7 after the last weekly CT, 4 months after inclusion, 3 weeks after end of CT and 1, 2 and 3 years after inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete remissions	Number of histologically proven complete remissions (ypT0ypN0 bzw. ypT0/is) after neoadjuvant CT	From date of randomization until the date of surgery
Millar Payne classification	Histological classification according to Millar Payne scale	after surgery/histological examination, an average 6 months after intervention start

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Trial outcome index score (TOI)	TOI	Date of inclusion (baseline), day -2 and +7 at each chemotherapy (CT) in triweekly cycles/-2 days at each CT in weekly cycles and +7 after the last weekly CT, 4 months after inclusion, 3 weeks after end of CT and 1, 2 and 3 years after inclusion
Total AC (FACT-B/FACT-O)	According to kind of cancer (breast cancer/ ovarian cancer)	Date of inclusion (baseline), day -2 and +7 at each CT in triweekly cycles/-2 days at each CT in weekly cycles and +7 after the last weekly CT, 4 months after inclusion, 3 weeks after end of CT and 1, 2 and 3 years after inclusion
FACIT-F	Fatigue	Date of inclusion (baseline), day -2 and +7 at each CT in triweekly cycles/-2 days at each CT in weekly cycles and +7 after the last weekly CT, 4 months after inclusion, 3 weeks after end of CT and 1, 2 and 3 years after inclusion
FACT-Tax,FACT/GynecologicOncologyGroup-Ntx	Specific chemotherapy induced effects on quality of life and neurologic symptoms	Date of inclusion (baseline), day -2 and +7 at each CT in triweekly cycles/-2 days at each CT in weekly cycles and +7 after the last weekly CT, 4 months after inclusion, 3 weeks after end of CT and 1, 2 and 3 years after inclusion
Chemotherapy-Induced Peripheral Neuropathy Assessment Tool	Chemotherapy-Induced Peripheral Neuropathy Assessment Tool	Date of inclusion (baseline), day -2 and +7 at each CT in triweekly cycles/-2 days at each CT in weekly cycles and +7 after the last weekly CT, 4 months after inclusion, 3 weeks after end of CT and 1, 2 and 3 years after inclusion
Hospital Anxiety and Depression Scale	Hospital Anxiety and Depression Scale	Date of inclusion (baseline), day -2 and +7 at each CT in triweekly cycles/-2 days at each CT in weekly cycles and +7 after the last weekly CT, 4 months after inclusion, 3 weeks after end of CT and 1, 2 and 3 years after inclusion
Side effects of CT	Likert scales	Date of inclusion (baseline), day -2 and +7 at each CT in triweekly cycles/-2 days at each CT in weekly cycles and +7 after the last weekly CT, 4 months after inclusion, 3 weeks after end of CT and 1, 2 and 3 years after inclusion
Weight	Documentation according to the standard documentation rules of the German Tumour Centres Work Group, Weight in kilograms	Timing varies according to individual therapy plan, Date of inclusion (baseline) and up to 3 years after inclusion
BMI	Documentation according to the standard documentation rules of the German Tumour Centres Work Group, BMI in kg/m^2	Timing varies according to individual therapy plan, Date of inclusion (baseline) and up to 3 years after inclusion
Blood panel	Documentation according to the standard documentation rules of the German Tumour Centres Work Group, units auf measure according to SI units	Timing varies according to individual therapy plan, Date of inclusion (baseline) and up to 3 years after inclusion
Blood values for liver function	Documentation according to the standard documentation rules of the German Tumour Centres Work Group, units auf measure according to SI units	Timing varies according to individual therapy plan, Date of inclusion (baseline) and up to 3 years after inclusion
Blood values for renal function (Krea, Hst.)	Documentation according to the standard documentation rules of the German Tumour Centres Work Group, units auf measure according to SI units	Timing varies according to individual therapy plan, Date of inclusion (baseline) and up to 3 years after inclusion
IGF-1, Insulin, Blood glucose	Explorative measurements in blood samples in subgroup of 20 patients	Baseline, after 4 months and before each of the first 4 CTs meaning approx week 1,4,7 and 10 after intervention start
Long-term explorative measurements: frequency of recurrence	Information taken from the documentation of the treatment, visits and questionnaires	1, 2 and 3 years after baseline
Long-term explorative measurements: e.g. polyneuropathy, cardiomyopathy	Information taken from the documentation of the treatment, visits, questionnaires and interview	1, 2 and 3 years after baseline
ketone bodies	Explorative measurements in capillary blood, only in subpopulation of n=20	Baseline, after 4 months and before each of the first 4 CTs meaning approx week 1,4,7 and 10 after intervention start
Elective items of the "Common Terminology Criteria for Adverse Events (CTCAE)	Elective items of the "Common Terminology Criteria for Adverse Events (CTCAE)"	Baseline, 3 weeks after end of CT, 1,2,3 years after baseline
Qualitative interviews in focus groups	Qualitative interviews in focus groups	Baseline, 6 months

Collaborators and Investigators

• Sponsor: Charite University, Berlin, Germany
• Investigators: Principal Investigator: Andreas Michalsen, Prof. Dr., Study Principal Investigator Charite

Publications and helpful links

General Publications

• Koppold-Liebscher D, Kessler CS, Steckhan N, Bahr V, Kempter C, Wischnewsky M, Hubner M, Kunz B, Paul M, Zorn S, Sari S, Jeitler M, Stange R, Michalsen A. Short-term fasting accompanying chemotherapy as a supportive therapy in gynecological cancer: protocol for a multicenter randomized controlled clinical trial. Trials. 2020 Oct 15;21(1):854. doi: 10.1186/s13063-020-04700-9.

Study record dates

Study Major Dates

• Study Start (Actual): May 10, 2017
• Primary Completion (Anticipated): June 10, 2025
• Study Completion (Anticipated): June 10, 2025

Study Registration Dates

• First Submitted: May 10, 2017
• First Submitted That Met QC Criteria: May 18, 2017
• First Posted (Actual): May 22, 2017

Study Record Updates

• Last Update Posted (Estimate): December 13, 2022
• Last Update Submitted That Met QC Criteria: December 12, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Fasting; Vegan
• Other Study ID Numbers: FIT 2

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No